Wednesday, March 9, 2016

Alpha-7 Agonist Found to Improve Cognition in Non-Smoking Patients With Schizophrenia

A study published in AJP in Advance suggests ABT-126—a selective alpha-7 (α7) nicotinic receptor partial agonist—may help improve cognition in patients with schizophrenia, but the medication showed significant effects only in those who were nonsmokers.

Although current therapies for schizophrenia have been shown to significantly improve positive symptoms of the disorder, none of them noticeably improves cognition. Previous studies suggest that α7 neuronal nicotinic receptors play a key role in cognitive function, and trials of ABT-126 suggest the medication is well tolerated by patients with Alzheimer’s disease and schizophrenia (up to 150 mg once daily).

To assess the effectiveness and safety of ABT-126 in the treatment of cognitive impairment, researchers from Cairo University in Egypt and AbbVie Inc., manufacturer of ABT-126, randomly assigned 207 clinically stable patients with schizophrenia to receive 10 mg of ABT-126, 25 mg of ABT-126, or placebo once daily for 12 weeks. The primary efficacy measure was the change from baseline to study endpoint on the MATRICS Consensus Cognitive Battery (MCCB) composite score. Secondary measures included changes in specific domains scores on the MCCB such as verbal learning and working memory.

The researchers found that ABT-126 demonstrated a dose-dependent improvement on cognition that trended toward but did not achieve statistical significance in the 165 patients who completed the trial. Additional subset analyses revealed that nonsmokers taking ABT-126 showed a significant improvement in overall MCCB scores compared with placebo, whereas smokers taking ABT-126 did not. In addition, nonsmokers treated with 25 mg of ABT-126 showed significant improvements in domain scores for verbal learning, working memory, and attention/vigilance.

“No meaningful changes in the severity of schizophrenia symptoms, as measured by the PANSS and its positive and negative symptom subscales, and specifically negative symptoms, as measured by the Negative Symptom Assessment, were observed in the total sample or in subgroups defined by smoking status or baseline level of negative symptoms,” the researchers added. “These results suggest that the improvements in cognition during treatment with ABT-126 were independent of changes in schizophrenia symptoms and that ABT-126 did not worsen the underlying psychotic illness.”

The researchers hypothesized that chronic nicotine exposure from tobacco smoke may render nicotinic receptors ineffective, but noted more research is needed to evaluate the effectiveness of ABT-126 in smokers and nonsmokers.

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